MRI parameters for predicting the effect of ultrasound-guided high-intensity focused ultrasound in the ablation of uterine fibroids.

AIM: To study the value of magnetic resonance imaging (MRI) parameters in predicting the efficacy of ultrasonic ablation of fibroids. MATERIALS AND METHODS: A total of 91 patients were divided into groups based on non-perfused volume (NPV) ratio and blood supply type. The preoperative MRI parameters were measured and analysed. A correlation analysis between the MRI parameters and the NPV ratio was performed. Receiver operating characteristic (ROC) curves were used to analyse and determine the cut-off value of MRI parameters to predict the ablation rate of fibroids. RESULTS: The uterine fibroids group with an NPV ratio <80% and the group with an NPV ratio of ≥80% had significant differences in signal intensity (SI) at MRI T2-weighted imaging (WI), fibroid-to-rectus abdominis SI ratio (SIR) at T2WI, and blood supply type (p<0.05). There were no significant differences in fibroid volume, T2WI signal uniformity, and apparent diffusion coefficient (ADC) values. The ADC value and SI and SIR at MRI T2WI in the group with poor blood supply were lower than those in the group with a rich blood supply (p<0.05). SI at MRI T2WI correlated negatively with the NPV ratio. The cut-off values for SI and SIR at MRI T2WI of fibroids whose NPV ratio exceeds 80% were 220.58 and 1.315, respectively. CONCLUSION: SI at MRI T2WI and blood supply type could be predictors of the efficacy of ablation. Ultrasonic ablation of fibroids with MRI T2WI hyperintensity and a rich blood supply had poor efficacy.

[Combination of CT mulitplane 3D reconstruction, radial endobronchial ultrasound and rapid on-site evaluation for diagnosing peripheral solitary pulmonary nodules].

Objective: To evaluate the diagnostic efficiency of combination of CT multiplane 3D reconstruction (CT-3DR), radial endobronchial ultrasound (R-EBUS), and rapid on-site evaluation (ROSE) for peripheral solitary pulmonary nodules (SPN). Methods: A total of 176 patients with peripheral solitary pulmonary nodule were included from the Nanjing Chest Hospital from March 2016 to March 2017. According to different methods, all the patients were divided into four groups: EG (i.e. R-EBUS+Guiding sheath (GS))group, CTE (i.e. CT-3DR+R-EBUS) group, RE (i.e. ROSE+R-EBUS) group, and triad (i.e. CT-3DR+ROSE+R-EBUS) group. Sampling was performed by transbronchial lung biopsy. The diagnostic yield and complications, procedure time and influencing factors in these four groups were retrospectively analyzed. The value of ROSE and combination of CT-3DR+ROSE+R-EBUS in diagnosis for SPN also was evaluated. Results: The diagnostic yield for total SPNs among four groups were 70.5% in EG group, 70.0% in CTE group, 69.0% in RE group and 74.0% in triad group, respectively. There was no significant difference among four groups (all P>0.05). The procedure time of EG group, CTE group, RE group and triad group were (34.0±6.3), (26.6±6.8), (27.2±7.8) and (19.4±5.4) min, respectively. The procedure time was the shortest in triad group compared with the other three groups (all P<0.001) and the time of CTE and RE groups were significantly shorter than the EG group (both P<0.001). The coincidence rates of CT-3DR navigation position with target bronchus were 87.5% in CTE group and 90.0% in triad group with no significant difference between these two groups (P>0.05). The diagnostic yield was higher for SPNs with their major diameter ≥2 cm than those with their major diameter<2 cm in all four groups (all P<0.05). The positive diagnostic yield was higher with ultrasonic probe located within SPN lesion than the probe adjacent to or deviated the lesion in all four groups (all P<0.05). In EG and RE groups, for those SPNs with the distance between the lesion and pleura≥2 cm, the diagnostic yield were higher than those withe the distance<2 cm (P<0.05) but no similar phenomenon was observed in CTE and triad groups. No significant correlation was detected between the diagnostic yield and the density of SPN lesions among four groups (all P>0.05). ROSE was used in RE and triad groups. The coincidence rate of ROSE with histopathology was 82.6% and the value of Kappa was 0.608. The diagnostic sensitivity, specificity, positive predictive value and negative predictive value of ROSE were 0.818, 0.846, 0.931 and 0.647, respectively. Conclusions: CT-3DR navigation and ROSE help to improve the diagnostic efficiency of R-EBUS for SPN. Combination of CT-3DR, R-EBUS and ROSE is of diagnostic value for peripheral SPN and with significant shortening of procedure time.

Phylogeny of dermatophytes with genomic character evaluation of clinically distinct Trichophyton rubrum and T. violaceum.

Trichophyton rubrum and T. violaceum are prevalent agents of human dermatophyte infections, the former being found on glabrous skin and nail, while the latter is confined to the scalp. The two species are phenotypically different but are highly similar phylogenetically. The taxonomy of dermatophytes is currently being reconsidered on the basis of molecular phylogeny. Molecular species definitions do not always coincide with existing concepts which are guided by ecological and clinical principles. In this article, we aim to bring phylogenetic and ecological data together in an attempt to develop new species concepts for anthropophilic dermatophytes. Focus is on the T. rubrum complex with analysis of rDNA ITS supplemented with LSU, TUB2, TEF3 and ribosomal protein L10 gene sequences. In order to explore genomic differences between T. rubrum and T. violaceum, one representative for both species was whole genome sequenced. Draft sequences were compared with currently available dermatophyte genomes. Potential virulence factors of adhesins and secreted proteases were predicted and compared phylogenetically. General phylogeny showed clear gaps between geophilic species of Arthroderma, but multilocus distances between species were often very small in the derived anthropophilic and zoophilic genus Trichophyton. Significant genome conservation between T. rubrum and T. violaceum was observed, with a high similarity at the nucleic acid level of 99.38 % identity. Trichophyton violaceum contains more paralogs than T. rubrum. About 30 adhesion genes were predicted among dermatophytes. Seventeen adhesins were common between T. rubrum and T. violaceum, while four were specific for the former and eight for the latter. Phylogenetic analysis of secreted proteases reveals considerable expansion and conservation among the analyzed species. Multilocus phylogeny and genome comparison of T. rubrum and T. violaceum underlined their close affinity. The possibility that they represent a single species exhibiting different phenotypes due to different localizations on the human body is discussed.

The role of melanin pathways in extremotolerance and virulence of Fonsecaea revealed by de novo assembly transcriptomics using illumina paired-end sequencing.

Melanisation has been considered to be an important virulence factor of Fonsecaea monophora. However, the biosynthetic mechanisms of melanisation remain unknown. We therefore used next generation sequencing technology to investigate the transcriptome and digital gene expression data, which are valuable resources to better understand the molecular and biological mechanisms regulating melanisation in F. monophora. We performed de novo transcriptome assembly and digital gene expression (DGE) profiling analyses of parent (CBS 122845) and albino (CBS 125194) strains using the Illumina RNA-seq system. A total of 17 352 annotated unigenes were found by BLAST search of NR, Swiss-Prot, Gene Ontology, Clusters of Orthologous Groups and Kyoto Encyclopedia of Genes and Genomes (KEGG) (E-value <1e‒5). A total of 2 283 unigenes were judged to be the differentially expressed between the two genotypes. We identified most of the genes coding for key enzymes involved in melanin biosynthesis pathways, including polyketide synthase (pks), multicopper oxidase (mco), laccase, tyrosinase and homogentisate 1,2-dioxygenase (hmgA). DEG analysis showed extensive down-regulation of key genes in the DHN pathway, while up-regulation was noted in the DOPA pathway of the albino mutant. The transcript levels of partial genes were confirmed by real time RT-PCR, while the crucial role of key enzymes was confirmed by either inhibitor or substrate tests in vitro. Meanwhile, numbers of genes involved in light sensing, cell wall synthesis, morphology and environmental stress were identified in the transcriptome of F. monophora. In addition, 3 353 SSRs (Simple Sequence Repeats) markers were identified from 21 600 consensus sequences. Blocking of the DNH pathway is the most likely reason of melanin deficiency in the albino strain, while the production of pheomelanin and pyomelanin were probably regulated by unknown transcription factors on upstream of both pathways. Most of genes involved in environmental tolerance to oxidants, irradiation and extreme temperatures were also assembled and annotated in transcriptomes of F. monophora. In addition, thousands of identified cSSR (combined SSR) markers will favour further genetic linkage studies. In conclusion, these data will contribute to understanding the regulation of melanin biosynthesis and help to improve the studies of pathogenicity of F. monophora.

Structural chromosomal abnormalities in couples in cases of recurrent spontaneous abortions in Jilin Province, China.

Recurrent spontaneous abortions (RSAs) occur in approximately 15 to 20% of all clinically recognizable pregnancies. Structural chromosome abnormalities result in increased risk of pregnancy loss. Parental chromosomal abnormalities are an important genetic cause of RSAs. Some cytogenetic investigations have been performed in various countries and regions to determine the pattern of chromosomal abnormalities in parents with RSAs. The aim of this study was to report the prevalence and type of structural chromosomal abnormalities in couples in cases of RSAs in Jilin Province, China. The prevalence of structural chromosomal abnormalities in these couples was 2.98%. The number of female carriers with balanced chromosomal aberrations significantly exceeded that of such male carriers, and the ratio of female/male carriers was approximately 2:1. The number of abortions in the case of female carriers was more than that for male carriers before the structural chromosome abnormality was diagnosed. This indicates that genetic counseling for couples with structural chromosomal abnormalities should consider the gender of the carriers.

In vitro antifungal susceptibility of Trichophyton violaceum isolated from tinea capitis patients.

OBJECTIVES: Trichophyton violaceum is an anthropophilic dermatophyte that is endemic to parts of Africa and Asia and is sporadic in Europe. T. violaceum mainly causes tinea capitis in both children and adolescents. Although the infections caused by T. violaceum are of considerable medical importance, its antifungal susceptibility profile remains poorly examined. METHODS: In this study, we tested the in vitro antifungal susceptibility of a set of clinical T. violaceum isolates obtained from tinea capitis patients, using the CLSI broth microdilution method. We tested eight antifungals and used isolates collected from Western China (21), Eastern China (12), the Middle East (1), Europe (20), South Africa (7) and Canada (1). RESULTS: The geometric means of the MICs of the antifungals for all isolates were as follows (in increasing order): posaconazole, 0.021 mg/L; terbinafine, 0.023 mg/L; voriconazole, 0.062 mg/L; amphotericin B, 0.20 mg/L; itraconazole, 0.34 mg/L; caspofungin, 0.56 mg/L; fluconazole, 4.23 mg/L; and flucytosine, 8.46 mg/L. No statistically significant differences in the susceptibility profiles of T. violaceum were detected within the geographical regions tested. CONCLUSIONS: Posaconazole, terbinafine and voriconazole were shown to be the most potent antifungal agents against T. violaceum isolates obtained from tinea capitis patients worldwide. These results might help clinicians in developing appropriate therapies that have a high probability of successfully treating tinea capitis due to T. violaceum.

Molecular cloning and characterization of a novel Y-box gene from Sepiella maindroni.

Y-box proteins are a family of highly conserved nucleic acid binding proteins that interact with genome and transcription product to modulate the transcriptional and translational processes. In the present study, a complete mRNA of Y-box binding protein (designated SmYB) was obtained from Sepiella maindroni by amplification of flanking sequences. The full size of SmYB cDNA was 1502 bp, including 99 bp at the 5ꞌ untranslated region (UTR), a 3ꞌ UTR of 821 bp with a poly (A) tail, and an open reading frame of 582 bp, encoding a polypeptide of 193 amino acids with the predicted molecular weight of 16.48 kDa. The conserved cold-shock domain and two known RNA binding motifs identified in SmYB strongly suggested that SmYB was a new member of Y-box proteins. Quantitative real-time PCR was performed to examine the expression of SmYB mRNA in various tissues, embryos, and its temporal expression in liver after cold shock. The mRNA transcript of SmYB was detected in all examined tissues, with the highest expression level in testis and ovary. SmYB was abundant in early developmental stages of S. maindroni embryos but diminished in the late post-embryonic development. In addition, cold-shock treatment upregulated the transcription of SmYB mRNA in liver. These results demonstrated that SmYB is involved in embryonic development of S. maindroni and its tolerance to acute low temperatures.

HER2, MET and FGFR2 oncogenic driver alterations define distinct molecular segments for targeted therapies in gastric carcinoma.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer deaths worldwide. Since the approval of trastuzumab, targeted therapies are emerging as promising treatment options for the disease. This study aimed to explore the molecular segmentation of several known therapeutics targets, human epidermal growth factor receptor 2 (HER2), MET and fibroblast growth factor receptor 2 (FGFR2), within GC using clinically approved or investigational kits and scoring criteria. Knowledge of how these markers are segmented in the same cohort of GC patients could improve future clinical trial designs. METHODS: Using immunohistochemistry (IHC) and FISH methods, overexpression and amplification of HER2, FGFR2 and MET were profiled in a cohort of Chinese GC samples. The correlations between anti-tumour sensitivity and the molecular segments of HER2, MET and FGFR2 alterations were further tested in a panel of GC cell lines and the patient-derived GC xenograft (PDGCX) model using the targeted inhibitors. RESULTS: Of 172 GC patients, positivity for HER2, MET and FGFR2 alternations was found in 23 (13.4%), 21 (12.2%) and 9 (5.2%) patients, respectively. Positivity for MET was found in 3 of 23 HER2-positive GC patients. Co-positivity for FGFR2 and MET was found in 1 GC patient, and amplification of the two genes was found in different tumour cells. Our study in a panel of GC cell lines showed that in most cell lines, amplification or high expression of a particular molecular marker was mutually exclusive and in vitro sensitivity to the targeted agents lapatinib, PD173074 and crizotinib was only observed in cell lines with the corresponding high expression of the drugs' target protein. SGC031, an MET-positive PDGCX mouse model, responded to crizotinib but not to lapatinib or PD173074. CONCLUSIONS: Human epidermal growth factor receptor 2, MET and FGFR2 oncogenic driver alterations (gene amplification and overexpression) occur in three largely distinct molecular segments in GC. A significant proportion of HER2-negative patients may potentially benefit from MET- or FGFR2-targeted therapies.

FGFR2 amplification has prognostic significance in gastric cancer: results from a large international multicentre study.

BACKGROUND: In preclinical gastric cancer (GC) models, FGFR2 amplification was associated with increased tumour cell proliferation and survival, and drugs targeting this pathway are now in clinical trials. METHODS: FGFR2 FISH was performed on 961 GCs from the United Kingdom, China and Korea, and the relationship with clinicopathological data and overlap with HER2 amplification were analysed. RESULTS: The prevalence of FGFR2 amplification was similar between the three cohorts (UK 7.4%, China 4.6% and Korea 4.2%), and intratumoral heterogeneity was observed in 24% of FGFR2 amplified cases. FGFR2 amplification was associated with lymph node metastases (P<0.0001). FGFR2 amplification and polysomy were associated with poor overall survival (OS) in the Korean (OS: 1.83 vs 6.17 years, P=0.0073) and UK (OS: 0.45 vs 1.9 years, P<0.0001) cohorts, and FGFR2 amplification was an independent marker of poor survival in the UK cohort (P=0.0002). Co-amplification of FGFR2 and HER2 was rare, and when high-level amplifications did co-occur these were detected in distinct areas of the tumour. CONCLUSION: A similar incidence of FGFR2 amplification was found in Asian and UK GCs and was associated with lymphatic invasion and poor prognosis. This study also shows that HER2 and FGFR2 amplifications are mostly exclusive.

[Safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy: A prospective, multi-center, single arm trial].

Objective: To evaluate the safety of double and a half layered esophagojejunal anastomosis in radical gastrectomy. Methods: This prospective, multi-center, single-arm study was initiated by the Affiliated Cancer Hospital of Zhengzhou University in June 2021 (CRAFT Study, NCT05282563). Participating institutions included Nanyang Central Hospital, Zhumadian Central Hospital, Luoyang Central Hospital, First Affiliated Hospital of Henan Polytechnic University, First Affiliated Hospital of Henan University, Luohe Central Hospital, the People's Hospital of Hebi, First People's Hospital of Shangqiu, Anyang Tumor Hospital, First People's Hospital of Pingdingshan, and Zhengzhou Central Hospital Affiliated to Zhengzhou University. Inclusion criteria were as follows: (1) gastric adenocarcinoma confirmed by preoperative gastroscopy;(2) preoperative imaging assessment indicated that R0 resection was feasible; (3) preoperative assessment showed no contraindications to surgery;(4) esophagojejunostomy planned during the procedure; (5) patients volunteered to participate in this study and gave their written informed consent; (6) ECOG score 0-1; and (7) ASA score I-III. Exclusion criteria were as follows: (1) history of upper abdominal surgery (except laparoscopic cholecystectomy);(2) history of gastric surgery (except endoscopic submucosal dissection and endoscopic mucosal resection); (3) pregnancy or lactation;(4) emergency surgery for gastric cancer-related complications (perforation, hemorrhage, obstruction); (5) other malignant tumors within 5 years or coexisting malignant tumors;(6) arterial embolism within 6 months, such as angina pectoris, myocardial infarction, and cerebrovascular accident; and (7) comorbidities or mental health abnormalities that could affect patients' participation in the study. Patients were eliminated from the study if: (1) radical gastrectomy could not be completed; (2) end-to-side esophagojejunal anastomosis was not performed during the procedure; or (3) esophagojejunal anastomosis reinforcement was not possible. Double and a half layered esophagojejunal anastomosis was performed as follows: (1) Open surgery: the full thickness of the anastomosis is continuously sutured, followed by embedding the seromuscular layer with barbed or 3-0 absorbable sutures. The anastomosis is sutured with an average of six to eight stitches. (2) Laparoscopic surgery: the anastomosis is strengthened by counterclockwise full-layer sutures. Once the anastomosis has been sutured to the right posterior aspect of the anastomosis, the jejunum stump is pulled to the right and the anastomosis turned over to continue to complete reinforcement of the posterior wall. The suture interval is approximately 5 mm. After completing the full-thickness suture, the anastomosis is embedded in the seromuscular layer. Relevant data of patients who had undergone radical gastrectomy in the above 12 centers from June 2021 were collected and analyzed. The primary outcome was safety (e.g., postoperative complications, and treatment). Other studied variables included details of surgery (e.g., surgery time, intraoperative bleeding), postoperative recovery (postoperative time to passing flatus and oral intake, length of hospital stay), and follow-up conditions (quality of life as assessed by Visick scores). Result: [1] From June 2021 to September 2022,457 patients were enrolled, including 355 men and 102 women of median age 60.8±10.1 years and BMI 23.7±3.2 kg/m2. The tumors were located in the upper stomach in 294 patients, mid stomach in 139; and lower stomach in 24. The surgical procedures comprised 48 proximal gastrectomies and 409 total gastrectomies. Neoadjuvant chemotherapy was administered to 85 patients. Other organs were resected in 85 patients. The maximum tumor diameter was 4.3±2.2 cm, number of excised lymph nodes 28.3±15.2, and number of positive lymph nodes five (range one to four. As to pathological stage,83 patients had Stage I disease, 128 Stage II, 237 Stage III, and nine Stage IV. [2] The studied surgery-related variables were as follows: The operation was successfully completed in all patients, 352 via a transabdominal approach, 25 via a transhiatus approach, and 80 via a transthoracoabdominal approach. The whole procedure was performed laparoscopically in 53 patients (11.6%), 189 (41.4%) underwent laparoscopic-assisted surgery, and 215 (47.0%) underwent open surgery. The median intraoperative blood loss was 200 (range, 10-1 350) mL, and the operating time 215.6±66.7 minutes. The anastomotic reinforcement time was 2 (7.3±3.9) minutes for laparoscopic-assisted surgery, 17.6±1.7 minutes for total laparoscopy, and 6.0±1.2 minutes for open surgery. [3] The studied postoperative variables were as follows: The median time to postoperative passage of flatus was 3.1±1.1 days and the postoperative gastrointestinal angiography time 6 (range, 4-13) days. The median time to postoperative oral intake was 7 (range, 2-14) days, and the postoperative hospitalization time 15.8±6.7 days. [4] The safety-related variables were as follows: In total, there were 184 (40.3%) postoperative complications. These comprised esophagojejunal anastomosis complications in 10 patients (2.2%), four (0.9%) being anastomotic leakage (including two cases of subclinical leakage and two of clinical leakage; all resolved with conservative treatment); and six patients (1.3%) with anastomotic stenosis (two who underwent endoscopic balloon dilation 21 and 46 days after surgery, the others improved after a change in diet). There was no anastomotic bleeding. Non-anastomotic complications occurred in 174 patients (38.1%). All patients attended for follow-up at least once, the median follow-up time being 10 (3-18) months. Visick grades were as follows: Class I, 89.1% (407/457); Class II, 7.9% (36/457); Class III, 2.6% (12/457); and Class IV 0.4% (2/457). Conclusion: Double and a half layered esophagojejunal anastomosis in radical gastrectomy is safe and feasible.

Low-threshold plasmonic lasing based on high-Q dipole void mode in a metallic nanoshell.

We propose a novel type of plasmonic lasing nanostructure consisting of a metallic shell and a gain core. We demonstrate numerically that highly localized void modes of such metallodielectric core-shell nanoparticles have a very high quality factor. We found that the dipole void mode has a lasing threshold as low as 128 cm(-1) at 800 nm as a result of the unique mode distribution within the shell, due to a maximum field enhancement around the void center. The lasing condition for a symmetry-reduced silver nanocup is also investigated and the low plasmonic lasing threshold is sustained provided that the opening angle of the nanocup is smaller than 10°. Our proposal presents a new path toward plasmonic lasers with low gain threshold.

Vascular endothelial growth factor and soluble intercellular adhesion molecule-1 in lung adenocarcinoma with malignant pleural effusion: correlations with patient survival and pleural effusion control.

The mechanisms by which vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) contribute to lung cancer growth have not been fully elucidated. This study aimed to assess the role of VEGF and sICAM-1 in control of pleural effusions (PE) and survival in patients with primary human lung adenocarcinoma. Using enzyme-linked immunoadsorbent assay, the concentrations of VEGF and sICAM-1 were measured in pleural effusions and serum from a total of 79 lung adenocarcinoma patients with malignant pleural effusions (MPE) and 24 patients with tuberculosis. Data were correlated with the efficacy of MPE control and survival. Compared to patients with tuberculosis, the levels of VEGF and sICAM-1 in both PE and serum were significantly higher in patients with lung adenocarcinoma. Statistically significant correlation was observed between PE VEGF levels and MPE control. PE VEGF≥2760 pg/ml was used as a cut-off point for failure to MPE control (odds ratio=7.06; 95% confidence interval (CI), 2.40-20.78; P<0.001). The median progression-free survival (PFS) from response assessment was 3 months. In a multivariate analysis, PE VEGF (hazard ratio [HR], 1.16; 95% CI, 1.02-1.32), serum sICAM-1 (HR, 1.90; 95% CI, 1.17-3.07) were confirmed as independent prognostic factors for PFS. The levels of VEGF in PE can be used to predict the therapeutic efficacy in the control of MPE and this, together with serum level of sICAM-1 is potential survival factors in lung adenocarcinoma patients with MPE.

A case-control analysis and laboratory study of the two feet-one hand syndrome in two dermatology hospitals in China.

BACKGROUND: Two feet-one hand syndrome (bilateral plantar tinea pedis with coexistent unilateral tinea manuum) is commonly seen in dermatology clinics, but the cause of the unilateral hand involvement remains unresolved. AIMS: To investigate the unilateral hand involvement in this syndrome. METHODS: This was a case-control study. The experimental group comprised 113 patients with bilateral tinea pedis and unilateral tinea manuum and the control group comprised 44 patients with tinea pedis only, without tinea manuum. Clinical data were recorded and pathogens were identified by fungal examination. The predominant pathogen, Trichophyton rubrum, was genotyped by PCR amplification of tandem repeat elements from the ribosomal DNA nontranscribed spacer region. RESULTS: Scratching habits were significantly different between the groups, and there was a significant relationship between tinea manuum and the hand reportedly used to scratch the feet. In analysis of isolates from the feet and the involved hand, 94.5% of pairs were of the same species, and 80% of pairs had the same genotypes. CONCLUSIONS: Contact between hands and feet probably results in the transmission of dermatophytes from the feet to the scratching hand.

Extensive tinea capitis and corporis in a child caused by Trichophyton verrucosum.

A 3-year-old boy presented with multiple lesions of tinea corporis with dermatophytids, and subsequent inflammatory lesions with alopecia on the scalp. At the beginning, topical clobetasone butyrate was prescribed. The infection was diagnosed as dermatophytosis on the basis of positive direct microscopy and fungal culture. The etiological agent was isolated from all sampled sites and identified as Trichophyton verrucosum. Clonal nature of the infection was confirmed by random amplified polymorphic DNA (RAPD) analysis. The child lived in close vicinity of cattle. He was successfully treated with itraconazole.

Wnt3 knockdown sensitizes human non-small cell type lung cancer (NSCLC) cells to cisplatin via regulating the cell proliferation and apoptosis.

OBJECTIVE: Aberrant activation of (Wingless and mouse homolog Int-1) Wnt/ß-catenin signaling pathways closely involved in the occurrence and progression of several types of human malignancies. This research was undertaken to elucidate the important role of (Wingless and mouse homolog Int-1) in lung cancer. PATIENTS AND METHODS: Wnt3 expression in lung cancers and their respective normal tissues were examined by immunoblotting and immunohistochemistry. Then, Wnt3 was regulated with RNA interference (RNAi) technology in human lung cancer A549 cells, and the cell proliferation, cell cycle, cell invasion/metastasis, and apoptosis were evaluated. RESULTS: In all cases, Wnt3 expression was significantly elevated in lung cancers compared with normal tissues. Knocking down Wnt3 in A549 lung cancer cells by small interfering RNAs transfection led to a distinct reduction of Wnt3 in both transcript and protein levels. Knockdown of Wnt3 expression in lung cancer cells inhibited the expression of ß-catenin and cyclin D1 genes in Wnt/ß-catenin pathway. It also significantly blocked cellular proliferation, delayed cell cycle and suppressed cell invasion/metastasis, accompanied by a higher apoptosis rate. CONCLUSIONS: We conclude that the upregulation of Wnt3 plays a crucial role in lung tumorigenesis by inducing proliferation, migration, and invasion and inhibiting apoptosis of cancer cells. Wnt3 might be a potential target for the treatment of lung cancer.

Mitogen-activated protein kinase kinase 4 metastasis suppressor gene expression is inversely related to histological pattern in advancing human prostatic cancers.

We have shown recently (B. A. Yoshida et al., Cancer Res., 59: 5483-5487) that mitogen-activated protein kinase kinase 4 (MKK4) can suppress AT6.1 rat prostate cancer metastases in vivo. Evaluation of the expression of components of the MKK4 signaling cascade showed a loss or down-regulation of expression of MKK4 or c-Jun, a downstream mediator of MKK4, in six of eight human prostate cancer cell lines. Given these findings, we next assessed whether MKK4 dysregulation occurs during the development of clinical prostate cancer. Immunohistochemical studies showed high levels of MKK4 expression in the epithelial but not the stromal compartment of normal prostatic tissues. In neoplastic tissues, a statistically significant, direct, inverse relationship between Gleason pattern and MKK4 was established. These results demonstrate that MKK4 protein is consistently down-regulated during prostate cancer progression and support a role for dysregulation of its signaling cascade in clinical disease. To test the possibility that down-regulation of MKK4 protein is the result of allelic loss, metastatic prostate cancer lesions were examined for loss of heterozygosity (LOH) within the MKK4 locus (D17S969). These studies showed a 31% (5 of 16) LOH of MKK4 that is not associated with coding region mutations, which suggests that the nucleotide sequence of the gene in the remaining allele is infrequently mutated.

3D-QSAR analysis of a series of S-DABO derivatives as anti-HIV agents by CoMFA and CoMSIA.

In this study, we retrieved a series of 59 dihydroalkylthio-benzyloxopyrimidine (S-DABO) derivatives, which is a class of highly potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) reported from published articles, and analysed them with comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). Statistically significant three-dimensional quantitative structure-activity relationship (3D-QSAR) models by CoMFA and CoMSIA were derived from a training set of 46 compounds on the basis of the rigid body alignment. Further, the predictive ability of the QSAR models was validated by a test set of 13 compounds. Based on the information derived from CoMFA and CoMSIA contour maps, we have identified some steric and electrostatic features for improving the activities of these inhibitors, and we validated the 3D-QSAR results by a molecular docking method. On the basis of the obtained results, we designed a new series of S-DABO derivatives with high activities. Therefore, this study could be utilized to design more potent S-DABO analogues as anti-HIV agents.

Antiandrogen-induced cell death in LNCaP human prostate cancer cells.

Antiandrogens such as Casodex (Bicalutamide) are designed to treat advance stage prostate cancer by interfering with androgen receptor-mediated cell survival and by initiating cell death. Treatment of androgen sensitive, non-metastatic LNCaP human prostate cancer cells with 0-100 microM Casodex or 0-10 ng/ml TNF-alpha induces cell death in 20-60% of the cells by 48 h in a dose-dependent manner. In cells treated with TNF-alpha, this is accompanied by the loss of mitochondrial membrane potential (DeltaPsim) and cell adhesion. In contrast, cells treated with Casodex display loss of cell adhesion, but sustained mitochondrial dehydrogenase activity. Overexpression of Bcl-2 in LNCaP cells attenuates the induction of cell death by TNF-alpha but not Casodex, suggesting that mitochondria depolarization is not required for the induction of cell death by Casodex. While both TNF-alpha and Casodex-induced release of cytochrome c in LNCaP cell is predominantely associated with the translocation and cleavage of Bax, our data also suggest that Casodex induces cell death by acting on components downstream of decline of DeltaPsim and upstream of cytochrome c release. Furthermore, while induction of both caspase-3 and caspase-8 activities are observed in TNF-alpha and Casodex-treated cells, a novel cleavage product of procaspase-8 is seen in Casodex-treated cells. Taken together, these data support the hypothesis that Casodex induces cell death by a pathway that is independent of changes in DeltaPsim and Bcl-2 actions and results in an extended lag phase of cell survival that may promote the induction of an invasive phenotype after treatment.

Regional differences in serotonergic input to canine parasternal intercostal motoneurons.

There is a mediolateral gradient in activation of the parasternal intercostal (PI) muscle during inspiration. In the present study, we tested the hypotheses that serotonergic [5-hydroxytryptamine (5-HT)] input from descending central drive and/or intrinsic size-related properties of PI motoneurons leads to the differential activation of PI muscles. In dogs, PI motoneurons innervating the medial and lateral regions of the PI muscles at the T(3)-T(5) interspaces were retrogradely labeled by intramuscular injection of cholera toxin B subunit. After a 10-day survival period, PI motoneurons and 5-HT terminals were visualized by using immunohistochemistry and confocal imaging. There were no differences in motoneuron morphology among motoneurons innervating the medial and lateral regions of the PI muscle. However, the number of 5-HT terminals and the 5-HT terminal density (normalized for surface area) were greater in motoneurons innervating the medial region of the PI muscle compared with the lateral region. These results suggest that differences in distribution of 5-HT input may contribute to regional differences in PI muscle activation during inspiration and that differences in PI motoneuron recruitment do not relate to size.